The objective of this proposal is to develop methods for quantitating daily intake of nicotine, tar and carbon monoxide while smoking cigarettes or consuming smokeless tobacco. Consumption of nicotine will be assessed using pharmacokinetic data obtained after intravenous infusion of nicotine in combination with nicotine blood concentration data obtained over 24 hours while consuming tobacco. Tar (mutagen/carcinogen) consumption will be estimated by quantitation of urinary excretion of mutagens (by the Ames Salmonella/Mammalian Microsome test) and of mercapturic acid and other thioethers (reflecting conjugated carcinogen metabolities with alkylating potential). Using these methods, the effects of several experimental manipulations of rate of elimination or availability of nicotine (i.e., urinary acidification vs. alkalinization, low vs. high nicotine cigarettes, and use of nicotine chewing gum) on nicotine, tar and carbon monoxide consumption will be studied. In addition, consumption of nicotine and mutagenes/carcinogens while using smokeless tobacco will be studied. Studies will also include analyses of the influence of sex, inter-individual metabolic differences, and prestudy smoking behavior and typology on consumption of tobacco smoke constituents. Results of our studies will provide further information about potential health hazards of different tobacco products and a quantitative reassessment of the nicotine titration hypothesis. Results may also be applicable to designing more effective smoking cessation therapies.